Rifaximin vs Placebo for the Prevention of Encephalopathy in Patients Treated by TIPS

Cirrhosis Clinical Trial

— PRPET  

Official title:

Double Blind Randomized Study, Comparing Rifaximin vs Placebo for the Prevention of Encephalopathy in Patients Treated by TIPS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02016196
• Other study ID #: RC31/12/0551
• Status: Completed
• Phase: Phase 3
• Start date: September 2013
• Est. completion date: July 2017

Study information

• Verified date: April 2020
• Source: University Hospital, Toulouse
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

TIPS has been used for 20 years, as a means of reducing portal pressure in patients with cirrhosis and portal hypertension related complications. TIPS proved more effective than alternative treatments in controlling or preventing variceal bleeding and refractory ascites. The main drawback of the TIPS procedure is progressive overt hepatic encephalopathy (OHE). Three risk factors for post-TIPS OHE have been identified: age over 65 years, history of previous episodes of OHE, and Child-Pugh score equal to or over 10. However, the incidence of post-TIPS OHE in patients fulfilling these criteria remains close to 35 %.

Description:

TIPS has been used for 20 years, as a means of reducing portal pressure in patients with cirrhosis and portal hypertension related complications. TIPS proved more effective than alternative treatments in controlling or preventing variceal bleeding and refractory ascites. The main drawback of the TIPS procedure is progressive overt hepatic encephalopathy (OHE). Three risk factors for post-TIPS OHE have been identified: age over 65 years, history of previous episodes of OHE, and Child-Pugh score equal to or over 10. However, the incidence of post-TIPS OHE in patients fulfilling these criteria remains close to 35 %. Furthermore, the pathogenesis of HE in general but also in patients treated by TIPS is still not well understood. Therefore, there is a real challenge in discovering new molecular mechanisms involved in pathogenesis of OHE as well as new treatment to better prevent the risk of OHE in patients treated by TIPS. Observational and experimental studies suggest a microbiota's role in the mechanism of OHE and recently a non absorbable antibiotic has proven to reduce the risk of recurrence of OHE. However, the effect of this drug for the prevention of a first episode of OHE in patients treated by TIPS is not known. In addition, the mechanisms of the beneficial effect of rifaximin remain poorly understood.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 211
• Est. completion date: July 2017
• Est. primary completion date: July 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• cirrhosis with TIPS for ascit treatment or hydrothorax

• prevention digestive bleeding follow up portal hypertension -

• signed consent

Exclusion Criteria:

• hepatocellular carcinoma out of Milan criteria or palliative phase cancer

• Child Pugh score > 12

• TIPS indicated for other indication than bellow

• encephalopathy signs : asterixis or confusion

• Hypersensibility to rifaximin, or derivated of rifamycin

• Patients treated by same class antibacterial

• pregnant woman

• Patient with hepatic transplant

Related Conditions & MeSH terms

• Brain Diseases
• Cirrhosis

Intervention

Drug:
• Rifaximin
6 rifaximin caps of 200 mg morning and night, 15 days before and 6 months after TIPS --------------------------------------------------------------------------------
• placebo
6 placebo caps per day morning and night, during 15 days before TIPS and 6 months after TIPS

Locations

Country	Name	City	State
France	CHU Angers	Angers
France	Hôpital Jean Verdier	Bondy
France	CHU Bordeaux	Bordeaux
France	CHRU Lille	Lille
France	CHU Marseille	Marseille
France	CHU Nantes	Nantes
France	CHU Beaujon Clichy	Paris
France	CHU Saint-Antoine	Paris
France	Pitié Salpêtrière	Paris
France	CHU Poitiers	Poitiers
France	CHU Rennes	Rennes
France	UHToulouse	Toulouse
France	CHU Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Toulouse

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	First episode of overt encephalopathy in patients treated by TIPS	First episode of overt encephalopathy in patients treated by TIPS	6 months
Secondary	number of hospitalisation days	Number and days of hospitalisations for encephalopathy	6 months
Secondary	Frequency of kidney insufficiency	number of digestive bleeding follow up to portal hypertension, number of ascit punctions, frequency kidney insufficiency and hepatocellular carcinoma	6 months
Secondary	transplants, deaths	- number of transplants and deaths	6 months
Secondary	intestinal microbiota	Composition of intestinal microbiota in 30 patients (only UHToulouse)	6 months